The scientific goal of this work is to understand low-frequency function of the cochlea. The projects will utilize a novel functional measure - the auditory nerve overlapped waveform (ANOW) - which is thought to originate from apical cochlear nerve fibers in response to low-frequency stimuli of low- to moderate-level. In Aim 1 we will compare the cochlear frequency-place specificity of ANOW to several conventionally used functional measures of higher cochlear frequency places (e.g., otoacoustic emissions, compound action potentials) by inducing highly localized regions of cochlear dysfunction. This approach will utilize another novel technique in which nanoliter volumes of toxic pharmaceuticals are introduced into scala tympani from a pipette sealed into the scala wall. When delivered in this manner, the distribution with time and distance is dominated by diffusion that is slow, highly predictable, and can be calculated. Functional measures from individual ears during induced local dysfunction will demonstrate whether ANOW evoked from less than 1 kHz stimuli originates from neural fibers associated with apical turns. Origins of conventionally used measures at both higher frequencies were their generation region is well known and at their low-frequency limit (~1 to 2 kHz) where their generation regions are less specific will be compared. Additionally, we will quantify auditory sensitivity as frequency is lowered from mid-frequencies down to infrasonic frequencies using low-frequency biasing paradigms. In Aim 2 we will use ANOW to objectively quantify, for the first time, low-frequency auditory sensitivity of animal models of endolymphatic hydrops. Low-frequency hearing loss is a primary symptom of human Meniere's disease, of which endolymphatic hydrops is the underlying pathology. A battery of measures will be used to assess function in three different animal models of hydrops and our focus will be to quantify low-frequency sensitivity. We hypothesize that our new ANOW measure will detect changes to low-frequency function in the early stages of endolymphatic hydrops when conventional measures of higher-frequency function do not. These studies will provide a scientific foundation for a better understanding of apical cochlear function. PUBLIC HEALTH RELEVANCE: This proposal addresses a long standing problem of the lack of non-behavioral measures of low-frequency auditory function. Presently available objective tests cannot adequately quantify hearing loss in low-frequency regions associated with speech vowels. An objective test to quantify low-frequency hearing loss would help to accurately fit infant hearing aids and to assist in the diagnosis of Meniere's disease.